Interobserver variability in upgraded and non-upgraded BI-RADS 3 lesions.

AIM: To evaluate interobserver variability in the assessment of Breast Imaging-Reporting and Data System (BI-RADS) 3 mammographic lesions, and to determine if the initial evaluation of upgraded BI-RADS 3 lesions was appropriate. MATERIALS AND METHODS: Retrospective review of the mammography database (1/1/2004-12/31/2008) identified 1,188 screen-detected BI-RADS 3 lesions, 60 (5.1%) were upgraded to BI-RADS 4/5 during surveillance (cases). Cases were matched to 60 non-upgraded BI-RADS 3 lesions (controls) by lesion type, laterality, and year. Available studies were assessed separately by two radiologists blinded to outcomes. RESULTS: Eighty-two studies were available (43 cases, eight malignancies, and 39 controls). Reader 1 assessed 18/82 (22%) as BI-RADS 0, 13 cases, five controls; 35/82 (42.7%) as BI-RADS 2, 11 cases, 24 controls; 7/82 (8.5%) BI-RADS 3, four cases, three controls; 22/82 BI-RADS 4, 15 cases, seven controls. Reader 2 assessed 8/82 (9.8%) as BI-RADS 0, four cases, four controls; 27 (32.9%) BI-RADS 2, 11 cases, 16 controls; 33 (40.2%) BI-RADS 3, 19 cases, 14 controls; 14 (17%) BI-RADS 4, nine cases, five controls. For cancers, reader 1 assessed two BI-RADS 0, one BI-RADS 2, one BI-RADS 3, and four BI-RADS 4; reader 2 assessed two BI-RADS 2, four BI-RADS 3, and two BI-RADS 4. Reasons for BI-RADS 0 assessment included incomplete mammographic views, lack of ultrasound, and failure to include the lesion on follow-up imaging. Reasons for BI-RADS 4 assessment included suspicious morphology or instability. CONCLUSION: There is much interobserver variability in the assessment of BI-RADS 3 lesions. Many BI-RADS 3 lesions were judged as incompletely evaluated on blinded review.

Intentional examination of esophagus by narrow-band imaging endoscopy increases detection rate of cervical inlet patch.

Foci of heterotopic gastric mucosa have been identified at different sites in the human body and the most common location is the proximal esophagus which is referred to as cervical inlet patch (CIP). The true prevalence of CIP varies and it is usually incidental findings during endoscopy. Because CIP is always asymptomatic, it was believed to be of little clinical relevance. However, emerging studies have described the acid-secreting characteristics of heterotopic gastric mucosa and associations of CIP with gastroesophageal reflux disease (GERD). In addition, complications such as stricture, fistula, infection, mucosal hyperplasia, and malignant transformation have been reported. In this study, we investigated the prevalence of CIP, its associations with clinical manifestations, and the effect of intentional screening upper esophagus by magnifying endoscopy-narrow-band imaging (ME-NBI) system. Consecutive healthy adults who underwent panendoscopy were separated into two groups. Patients in group I (n = 471) were examined by an endoscopist who intended to find CIPs by ME-NBI. Patients in group II (n = 428) were examined by two endoscopists who were unaware of the study and performed white-light imaging endoscopy. Participants provided questionnaires on GERD-related symptoms. Higher CIP prevalence (11.7% vs. 1.9%, P < 0.0001) and longer duration of esophageal examination (mean ± standard deviation, 17.50 ± 12.40 vs. 15.24 ± 10.78 seconds, P = 0.004) were noted in group I than in group II. Analyzing group I patients revealed the higher prevalences of reflux symptoms (32.7% vs. 18.3%, P = 0.013) and erosive esophagitis (43.6% vs. 25.5%, P = 0.005) in patients with CIP than in those without. CIP was not associated with globus or dysphagia symptoms. More small CIPs (< 5 mm) were detected by ME-NBI than by white-light imaging (85.3% vs. 41.4%, P = 0.001). In conclusion, CIP prevalence was not low under intentional ME-NBI examination of the upper esophagus. The clinical relevance of CIP and its association with GERD require further investigation.

Tag single nucleotide polymorphisms of alcohol-metabolizing enzymes modify the risk of upper aerodigestive tract cancers: HapMap database analysis.

Although alcohol is associated with higher upper aerodigestive tract (UADT) cancer risk, only a small fraction of alcoholics develop cancers. There is a lack of evidence proving the association of tag single nucleotide polymorphisms of alcohol-metabolizing enzymes with cancer risk. The aim of this study was to determine the association of these genetic polymorphisms with UADT cancer risk in a Chinese population. It was a hospital-based case-control candidate gene study. The databases of the International HapMap Project were searched for haplotype tag single nucleotide polymorphisms of the genes alcohol dehydrogenase (ADH)1B, ADH1C, and aldehyde dehydrogenase (ALDH)2. The genotyping was performed by the Sequenom MassARRAY system. Totally, 120 head and neck squamous cell carcinoma, 138 esophageal squamous cell carcinoma patients, and 276 age- and gender-matched subjects were enrolled between June 2008 and June 2010.Minor alleles of ADH1B (rs1229984) and ALDH2(rs671) were not only associated with the risk of UADT cancers (odds ratio [OR] [95% confidence interval, CI]: 3.53 [2.14-5.80] and 2.59 [1.79-3.75], respectively) but also potentiated the carcinogenic effects of alcohol (OR [95% CI]: 53.44 [25.21-113.29] and 70.08 [33.65-145.95], respectively). Similar effects were observed for head/neck and esophageal cancer subgroups. Multivariate logistic regression analysis identified four significant risk factors, including habitual use of cigarettes, alcohol, betel quid, and lower body mass index (P < 0.001). The haplotypes GAGC (OR 1.61, 95% CI 1.08-2.40, P = 0.018) and CCAATG (OR 1.69, 95% CI 1.24-2.30, P < 0.001) on chromosomes 4 and 12, respectively, were associated with higher cancer risk. These findings suggested that risk allele or haplotype carriers who consume alcohol and other carcinogens should be advised to undergo endoscopy screening. The information can be used to determine the degree of susceptibility of each subject and can be combined with other environmental factors, like carcinogen consumption, in the screening analysis.

Advanced criticality assessment method for sewer pipeline assets.

For effective management of water and wastewater infrastructure, the United States Environmental Protection Agency (US-EPA) has long emphasized the significant role of risk in prioritizing and optimizing asset management decisions. High risk assets are defined as assets with a high probability of failure (e.g. soon to fail, old, poor condition) and high consequences of failure (e.g. environmental impact, high expense, safety concerns, social disruption). In practice, the consequences of failure are often estimated by experts through a Delphi method. However, the estimation of the probability of failure has been challenging as it requires the thorough analysis of the historical condition assessment data, repair and replacement records, and other factors influencing the deterioration of the asset. The most common predictor in estimating the probability of failure is calendar age. However, a simple reliance on calendar age as a basis for estimating the asset's deterioration pattern completely ignores the different aging characteristics influenced by various operational and environmental conditions. This paper introduces a new approach of using 'real age' in estimating the probability of failure. Unlike the traditional calendar age method, the real age represents the adjusted age based on the unique operational and environmental conditions of the asset. Depending on the individual deterioration pattern, the real age could be higher or lower than its calendar age. Using the concept of real age, the probability of failure of an asset can be more accurately estimated.

Routine cardiac evaluation in patients with ischaemic stroke and absence of known atrial fibrillation or coronary heart disease: transthoracic echocardiography vs. multidetector cardiac computed tomography.

BACKGROUND AND PURPOSE: Cardiac evaluation is routinely conducted in patients with ischaemic stroke because embolisms originating from the heart are an important cause of stroke. We compared the prevalence of cardioaortic sources of cerebral embolism (CSCE) in patients with ischaemic stroke detected by transthoracic echocardiography (TTE) and/or multidetector cardiac computed tomography (MDCT). Additionaly, we investigated the frequency and severity of asymptomatic coronary artery disease (CAD) in patients who underwent MDCT. METHODS: We prospectively recruited patients with non-atrial fibrillation-related stroke who had no history of cardiac disease. Patients underwent cardiac evaluation using TTE alone (N=243, during the early phase of this study--TTE period), TTE and MDCT (N=62, midphase--transitional period) and MDCT alone (N=138, late phase--MDCT period). CSCE were defined according to the original and revised TOAST classifications. CAD was defined as 50% or more stenosis of the coronary artery. RESULTS: Patients' characteristics did not differ amongst groups; however, CSCE were more frequently detected in the MDCT period than in the TTE period (18.1% vs. 6.6%, P<0.001). In the transitional period, there were 16 patients (25.8%) who were found to be CSCE by MDCT but not TTE, whilst three patients (4.8%) were found to be CSCE by TTE but not MDCT (P=0.004). Amongst the patients who underwent MDCT, 72 (36.0%) had asymptomatic CAD, invasive coronary angiography was needed in 21 (10.5%) and 10 (5.0%) patients finally underwent coronary intervention. CONCLUSION: Multidetector cardiac computed tomography proved to be complementary to TTE for the identification of CSCE and can detect asymptomatic CAD, one of the major causes of vascular death in patients with stroke, in patients with non-atrial fibrillation-related stroke.

Comparative study between endoscopic ultrasonography and positron emission tomography-computed tomography in staging patients with esophageal squamous cell carcinoma.

Treatment strategy of esophageal cancer mainly depends on accurate staging. At present, no single ideal staging modality is superior to another in preoperative tumor-node-metastasis (TNM) staging of patients with esophageal cancer. We aimed to investigate the efficacy of endoscopic ultrasonography (EUS) and positron emission tomography-computed tomography (PET-CT) for staging of esophageal cancer. We retrospectively studied 118 consecutive patients with esophageal squamous cell carcinoma who underwent esophagectomy with or without neoadjuvant chemoradiotherapy (CRT) over a near 3-year period between January 2005 and November 2008 at a tertiary hospital in Taiwan. Patients were separated into two groups: without neoadjuvant CRT (group 1, n= 28) and with CRT (group 2, n= 90). Medical records of demographic data and reports of EUS and PET-CT of patients before surgery were reviewed. A database of clinical staging by EUS and PET-CT was compared with one of pathological staging. The accuracies of T staging by EUS in groups 1 and 2 were 85.2% and 34.9%. The accuracies of N staging by EUS in groups 1 and 2 were 55.6% and 39.8%. The accuracies of T and N staging by means of PET-CT scan were 100% and 54.5% in group 1, and were 69.4% and 86.1% in group 2, respectively. In group 2, 38 of 90 patients (42.2%) achieved pathologic complete remission. Among them, two of 34 (5.9%) and 12 of 17 (70.6%) patients were identified as tumor-free by post-CRT EUS and PET-CT, respectively. EUS is useful for initial staging of esophageal cancer. PET-CT is a more reliable modality for monitoring treatment response and restaging. Furthermore, the accuracy of PET-CT with regard to N staging is higher in patients who have undergone CRT than those who have not.

VA TECHNOLOGY TRANSFER PROGRAM RESPONDS TO COVID-19 PANDEMIC.

The COVID-19 pandemic stressed healthcare systems all over the world. Two primary challenges that healthcare systems faced were a shortage of personal protective equipment and the need for new technologies to handle infection prevention for staff and patients. The Department of Veteran's Affairs (VA) Technology Transfer Program responded by prioritizing the development of innovations in the Technology Transfer Assistance Project which addressed the pandemic. This paper describes several innovations that addressed the needs of the VA healthcare system during the pandemic and how they were rapidly developed.

Vertebral artery dominance contributes to basilar artery curvature and peri-vertebrobasilar junctional infarcts.

OBJECTIVES: The diameters of the vertebral arteries (VAs) are very often unequal. Therefore, this study investigated if unequal VA flow contributes to the development of basilar artery (BA) curvature and if it is a link to the laterality of pontine or cerebellar infarcts occurring around the vertebrobasilar junction. METHODS: Radiological factors were analysed (infarct laterality, VA dominance, BA curvature and their directional relationships) in 91 patients with acute unilateral pontine or posterior inferior cerebellar artery (PICA) territory infarcts. The "dominant" VA side was defined as either that the VA was larger in diameter or the VA was connected with the BA in more of a straight line, if both VAs looked similar in diameter on CT angiography. Multiple regression analysis was performed to predict moderate to severe BA curvature. RESULTS: The dominant VA was more frequent on the left side (p<0.01). Most patients had an opposite directional relationship between the dominant VA and BA curvature (p<0.01). Pontine infarcts were opposite to the side of BA curvature (p<0.01) and PICA infarcts were on the same side as the non-dominant VA side (p<0.01). The difference in VA diameters was the single independent predictor for moderate to severe BA curvature (OR per 1 mm, 2.70; 95% CI 1.22 to 5.98). CONCLUSIONS: Unequal VA flow is an important haemodynamic contributor of BA curvature and development of peri-vertebrobasilar junctional infarcts.

Usefulness of a photophobia questionnaire in patients with migraine.

Photophobia is an important criterion for the diagnosis of migraine. However, several Asian epidemiological surveys about migraine have shown lesser prevalence of photophobia than that of Western studies. This discrepancy is probably caused by underestimation of photophobia due to inappropriate questioning of patients by physicians. To investigate this issue, we developed a questionnaire about photophobia and evaluated its usefulness in 103 patients with migraine. In phase 1 of the study, we found good repeatability of the questionnaire with a 0.826 kappa coefficient. In phase 2, the prevalence of photophobia from interviews and that from the questionnaire were compared. The prevalence of interview-documented photophobia was 51.5% and of questionnaire-documented photophobia 82.5% (P < 0.001). In phase 3, we attempted to make a short-form questionnaire with the same detection power of the questionnaire study. Two short-form questionnaires were identified as a useful method for detecting photophobia. The prevalence of photophobia could be underreported via interview, especially in Asian migraineurs. Using this questionnaire to test for photophobia, the diagnostic rate of photophobia and migraine could be improved.

Differential effects of corticosteroids on the expression of cyclooxygenase-2, tumour necrosis factor-alpha and matrix metalloproteinase-9 in an animal model of migraine.

Nitric oxide (NO) directly activates trigeminal afferents innervating the dura mater and up-regulates inflammatory mediators. We evaluated NO-mediated up-regulation of cyclooxygenase-2 (COX-2), tumour necrosis factor-alpha (TNF-alpha) and matrix metalloproteinase-9 (MMP-9), and the effect of glucocorticoid administration in an experimental animal model of migraine. COX-2 and TNF-alpha expression and MMP-9 activity were increased after continuous intravenous infusion of glyceryl trinitrate (GTN), a NO donor. Immunofluorescence staining demonstrated strong expression of these inflammatory mediators in the meningeal blood vessels. Methylprednisolone (MP) down-regulated MMP-9, which was reversed by RU486, a glucocorticoid receptor antagonist. COX-2 and TNF-alpha expression was not affected by MP or RU486 administration. These results suggest proinflammatory mediators are involved in the NO-mediated cascade of migraine pathogenesis. Further understanding of the activation of these inflammatory mediators at the transcriptional level may have therapeutic implications for future migraine treatments.

Transplantation After Successful Downstaging by Multimodal Treatments of American Joint Committee on Cancer Stage IIIB Hepatocellular Carcinoma With Portal Vein Thrombi: A Case Report.

The effective treatment for hepatocellular carcinoma (HCC) with American Joint Committee on Cancer stage IIIB remains controversial and challenging because of the high recurrence rate after resection and low survival rate. The median survival of those with macroscopic portal vein tumor thrombus (PVTT) is short. We reported such a case which received liver transplantation (LT) after successful consecutive downstaging therapies. A 40-year-old man with alcohol related liver cirrhosis and repeated esophageal varices bleeding had HCC with tumor thrombi in right main portal vein and the second portal branch of segment VI (stage IIIB). The received percutaneous alcohol injection, radiofrequency ablation, 8 sessions of transcatheter hepatic arterial chemoembolization, radiotherapy, and target therapy with sorafenib. Computed tomography (CT) scan and magnetic resonance imaging after treatments showed no viable fragments in the tumor and revealed both the right main portal vein and V1 branch were patent. One month later, the patient received a deceased LT. The perioperative course was rather smooth. After discharge, the interval follow-up CT studies of the chest and liver and whole body bone scan showed no tumor recurrence or metastasis up to 20 months postoperation.

Regulation of adipocyte differentiation by PEGylated all-trans retinoic acid: reduced cytotoxicity and attenuated lipid accumulation.

Obesity is major risk factor for many disorders, including diabetes, hypertension and heart disease. Unfortunately, there is a dearth of therapeutic agents available to clinicians for the treatment of obesity. The principal aim of this study was to investigate whether PEGylated all-trans retinoic acid (PRA) can have favorable stability and biological activity in 3T3-L1 preadipocytes as an antiobesity drug. Here, we found that PRA inhibits the process of adipogenesis, including survival of adipocytes and differentiation to mature adipocytes. The results showed that RA nanoparticles (NPs) were prepared by PEGylation; below 200 nm, PRA-NPs were obtained. Moreover, PRA decreased glycerol-3-phosphate dehydrogenase activity in 3T3-L1 preadipocytes by acting with major adipocyte marker proteins such as PPARgamma2, C/EBPalpha and aP2 modulators. Apoptosis, in addition, increased as the level of RA increased from 10 to 20 microM, whereas PRA reduced apoptosis with increasing concentrations. Our data suggest that PRA-NP has potential as an antiobesity drug carrier due to its small particle size and PEGylated core-shell structure. In addition, our results suggest that PRA inhibits the process of adipogenesis and may be developed to treat obesity. Based on these results, PRA is suitable for adipocyte studies, and an enhanced effect of PRA with adipocyte differentiation offers a challenging approach for pharmaceutical applications.

"Snowmelt Sign" and "Corkscrew Microvessels" Predicting Epithelium Regeneration After Acute Rejection of Small-Bowel Transplantation: A Case Report.

Intestinal failure characterized by inadequate maintenance of nutrition via normal intestinal function comprises a group of disorders with many different causes. If parenteral nutrition dependency develops, which is associated with higher mortality and complications, it is considered for intestine transplantation. However, the graft failure rate is not low, and acute cellular rejection is one of the most important reasons for graft failure. As a result, early identification of rejection and timely modification of anti-rejection medications have been considered to be associated with better graft and patient survival rates. The diagnostic gold standard for rejection is mainly based on histology, but hours of delay by pathology may occur. Some researchers investigated the association of endoscopic images with graft rejection to provide timely diagnosis. In this study, we present the first case report with characteristic features under magnifying endoscopy with a narrow-band imaging system to predict epithelial regeneration and improvement of graft rejection in a patient with small-bowel transplantation.

Preconception radiation, intrauterine diagnostic radiation, and childhood neoplasia.

Diagnostic X-ray examinations as a potential risk for neoplasia were investigated in a prospective study of 55,908 women who participated in the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke. The X-ray exposure histories of 145 mothers whose children developed neoplasms and 290 matched controls were examined. Of the childhood neoplasms, 40 were malignant and 105 were benign. Generally, the data were consistent with increased risk of malignant neoplasms among children of women exposed to X-rays before and during pregnancy, with a somewhat higher relative risk estimate for preconception exposure. No significant association of X-ray exposure and benign neoplasms was detected.

Early Detection of a Hepatic Artery Pseudoaneurysm After Liver Transplantation Is the Determinant of Survival.

BACKGROUND: Hepatic artery pseudoaneurysm (PA) after liver transplantation (LT) is a rare but potentially fatal complication. Among a series of 50 patients of LT, we experienced 3 such cases. Some authors also have reported cases of PA, either intrahepatic or extrahepatic. The aim of this study was to investigate the important factors that affect the treatment outcome. METHODS: Three patients were presented. To analyze the factors, not only our patients but also the patients with PA reported in the literature (including 10 case series and 23 case reports) were enrolled for analysis. The possible factors probably affecting the survival were compared statistically, including age, sex, clinical manifestation as bleeding (including gastrointestinal bleeding, hemobilia, or intra-abdominal bleeding), treatment (with embolization or surgical exploration or stent), diagnosis establishment before or after bleeding, and so forth. RESULTS: From univariate analysis, the significant factors that affect survival are sex (female) (P = .036), stent treatment (P = .006), and early detection (P = .036), whereas age (P = .493) and presentation with hemorrhage (P = .877) are not significant factors. However, according to multivariate analysis, stent treatment has a borderline significance (P = .056). CONCLUSIONS: Early detection of such a life-threatening complication is a key determinant of survival. "Early" does not refer to early postoperative days but means the detection prior to the rupture of the pseudoaneurysm. Postoperative imaging studies such as computed tomographic scan or magnetic resonance cholangiopancreatography early and periodically to follow up the graft status is recommended, especially for those who had received other interventions before or after the liver transplantation.

Proteasome participates in the alteration of signal transduction in T and B lymphocytes following trauma-hemorrhage.

Proteasomes are essential components of the cellular protein degradation machinery. They are nonlysosomal and their participation is critical for (1) the removal of short lived proteins involved in metabolic regulation and cell proliferation, (2) the control of the activities of regulators involved in gene transcription, such as nuclear factor-kappa B (NF-kappa B) and signal transducer and activator of transcription (STAT1), and (3) processing of antigenic peptides for MHC class I presentation. Trauma-hemorrhage induces profound immunosuppression which is characterized by reduced splenocyte proliferation, interleukin (IL)-2 and interferon (IFN)-gamma productive capacity, increased activation of transcription factors NF-kappa B and STAT1 in splenic T lymphocytes, reduced macrophage antigen presentation capacity and inordinate release of proinflammatory cytokines, such as IL-6 and tumor necrosis factor-alpha. Furthermore, it appears that the activity of several regulatory proteins involved in immune function is altered by trauma-hemorrhage. Since proteasomes are involved in regulation and removal of regulatory proteins, we hypothesized that trauma-hemorrhage alters proteasomal activity in splenic lymphocytes. The data showed that activities of 26s proteasome from CD3+CD4+ and CD3+CD8+ splenic T lymphocytes were enhanced following trauma-hemorrhage which was associated with increased expression of NF-kappa B and STAT1. On the other hand, trauma-hemorrhage attenuated the activity of 26s proteasome from splenic B lymphocytes which was restored upon IFN-gamma stimulation and correlated with increased expression of NF-kappa B. These studies indicate a potential role for proteasomes in the regulation of signal transduction in splenic T and B lymphocytes following trauma-hemorrhage, and also suggest them as potential therapeutic targets for attenuation of immune suppression associated with this form of injury.

Cancer and cardiac mortality among 15-year survivors of cancer diagnosed during childhood or adolescence.

PURPOSE: To evaluate the impact of cardiac disease and second malignant neoplasms on late mortality rate and to identify risk factors for late mortality among 15-year survivors of cancer diagnosed during childhood or adolescence. PATIENTS AND METHODS: Gender-specific all-cause and cause-specific (cardiac disease, cancer) standardized mortality ratios were calculated. Kaplan-Meier survival estimates and Cox regression analyses were performed to determine the relationship of several demographic and treatment variables to survival. RESULTS: Patients who survived for 15 years after diagnosis had excess subsequent all-cause, cancer (second malignant neoplasms only), and cardiac mortality rates. No decrease in the late mortality rate by treatment era (1960 to 1970, 1971 to 1984) was identified. Risk factors for males included disease recurrence during the first 15 years after diagnosis, treatment with doxorubicin, and the diagnosis of Hodgkin's disease. Those for females included treatment with radiation therapy, treatment with an alkylating agent, and disease recurrence during the first 15 years after diagnosis. Cox regression analysis demonstrated that only an initial duration of remission of less than 15 years (P <.01) and treatment with doxorubicin (P =.08) were significantly associated with shorter survival time for males. No variable was significantly associated with shorter survival time for females in Cox regression analysis. CONCLUSION: Fifteen-year survivors of childhood cancer have excess mortality. More effective treatments must be developed to reduce this excess risk. Fifteen-year relapse-free survivors did not have excess mortality. This group will require continued observation to determine whether excess mortality will become apparent as more events occur.

Sepsis-induced SOCS-3 expression is immunologically restricted to phagocytes.

We have shown that immune cells from septic mice exhibit a suppressed response to exogenous stimuli in vitro. The suppressors of the cytokine signaling (SOCS) family are proteins that block intracellular signaling and can be induced by inflammatory mediators. Therefore, we hypothesized that SOCS-3 is up-regulated in immune cells in response to a septic challenge induced by cecal ligation and puncture (CLP). Mice were subjected to CLP or sham-CLP, and 2-48 h later, the blood, thymus, spleen, lung, and peritoneal leukocytes were harvested and examined. SOCS-3 was undetectable in thymocytes or blood leukocytes. In contrast, SOCS-3 was up-regulated in the spleen, lung, and peritoneal leukocytes in a time-dependent manner. Further examination revealed that only the macrophages and neutrophils expressed SOCS-3. These data suggest that cytokines and bacterial toxins present during sepsis have the ability to suppress the cytokine and/or lipopolysaccharide response and the function of immune cells by up-regulating SOCS-3.